The syngeneic mixed leukocyte reaction represents polyclonal activation of antigen-specific T lymphocytes with receptors for self-Ia antigens.

We used a combination of positive and negative selection techniques to evaluate the relationship between the T cell that responds to self-Ia antigens in the SMLR and the T cells that respond to foreign antigen in association with self-Ia. BudR and light treatment of T cells proliferating in the SMLR abolished their subsequent primary and secondary proliferative response to antigen but had little effect on their response to allogeneic Ia. F1 cells that had been positively selected in the SMLR with stimulator cells from 1 parental strain demonstrated a markedly enhanced proliferative response to antigen in association with the parental strain used in the SMLR selection culture. The observed genetic restriction on the antigen responses of SMLR primed F1 T cells was not the result of haplotype-specific help or suppression and most likely represents direct activation of antigen-specific T cell clones by unmodified Ia antigens.